Much evidence supports a hypothesis that hypothalamic preoptic area (POA) temperature-sensitive neurons play a critical role in the regulation of NREM sleep, as a component of overall metabolic regulation. The activation of POA warm sensitive neurons is necessary and sufficient for initiation of NREM sleep. The hypnogenic output from the POA is hypothesized to be a descending gamma-aminobutyric acid (GABA)ergic pathway which inhibits arousal-promoting systems in the posterior hypothalamus (PH) and brainstem. In PH, a GABA-regulated system facilitates respiratory motor and autonomic responses. We hypothesize that PH respiratory mechanisms are coupled to PH arousal generating mechanisms, and that arousal induced respiratory facilitation originating in the PH is a critical component of the wakefulness-drive to-breathing. We propose a model in which this drive is actively inhibited during sleep, that this inhibition originates in the POA, and is mediated by GABAergic inhibitory projections from the POA to the PH. The proposed studies will examine hypothesis central to this model. Activation of POA warm-sensitive neurons will 1) suppress diaphragmatic and upper airway dilator activity during sleep and 2) suppress discharge of PH neurons in chronic animals, via a GABAergic process. 3) POA warming will reduce respiratory coupling of medullary reticular neurons. POA cooling will have opposite effects. Obstructive sleep apnea are characterize by sleep onset-induced airway dilator and respiratory pump muscle deactivation. These events are thought to be consequences of the loss of the wakefulness-drive-to-breathing. In addition, many patients exhibit reduced arousal responses and reduced compensation for airway resistance, Thus, we hypothesize that arousal dysregulation is part of the disease. We hypothesize that excessive energy conservation drive, originating in the POA, induces sleepiness and respiratory motor deactivation at sleep onset.